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Conrad Notes
a timely medical meeting newsletter
E. L. Gardner, PhD, Albert Einstein College of Medicine, Bronx, NY, described a pleasure/reward circuit of the mammalian brain. All drugs with addictive potential activate this neuronal circuit. The pleasure/reward areas of the brain are anatomically and neurochemically distinct from areas for physical dependence and withdrawal.
Neuroanatomy Experimental evidence supports a subcomponent of the mesolimbic dopaminergic circuit involved in drug abuse, addiction, and dependency. Anatomically, the circuit arises from Nucleus A10 (ventral tegmental area) in the ventral mesencephalon and ends in the nucleus accumbens of the ventral forebrain limbic area. This circuit modulates the hedonic tone of the central nervous system.
Physiology Electrical stimulation of the pleasure/reward circuit leads to increased self-reinforcement by laboratory animals. Two clinical experiments confirmed the pleasure experienced by stimulating the same circuit in humans.
Pharmacology Laboratory animals avidly self-administer recreational drugs to activate the pleasure/reward circuit. Direct microinjection into this brain circuit does the same. A corresponding lesion or application of a chemical blocker (e.g., a dopamine antagonist) prevents increased self-administration. Microdialysis sampling of the nucleus accumbens can detect minute amounts of dopamine released after electrical or chemical stimulation.
Genetic variation in drug taking Laboratory-bred rat strains vary in rates of self-injecting opiates, cocaine and other psychostimulants into the pleasure/reward area. Lewis rats like the recreational drugs and work harder at self-injecting than other strains. However, repeated exposure to recreational drugs can modestly increase the rate of self-injection by the other strains.
Human vulnerability What happens in the pleasure/reward circuitry to make a person more vulnerable to addiction? Vulnerability seems to depend on three factors. As seen in rat strain differences in self-administration, genetics may be the primary determinant. The timing of repeated administrations, coupled with exposure to stress, are major environmental influences. According to Gardner, present knowledge supports the interplay of these three factors in helping to understand individual vulnerability to addiction.

For professional correspondence, please contact Dr. Gardner at: gardner@aecom.yu.edu

Eugene A. Conrad

Presented at the Conference on Pain Management and Chemical Dependency on 22 Nov 1996
CONRAD NOTES © All Rights Reserved December 1996
Eugene A. Conrad, PhD, MPH / ISSN 1078 / posted on 1-Feb-1997

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